Antiepileptic medicine, together with valproic acid, lamotrigine, and gabapentin, are used for the therapy of temper and anxiousness signs throughout totally different psychiatric issues. We have now information to point that prenatal publicity to some AEDs, particularly valproic acid, not solely will increase threat for main malformations however is related to an elevated threat for hostile neurodevelopmental outcomes. A systematic review published in Neurology examines research assessing neurodevelopmental outcomes in kids prenatally uncovered to valproic acid and different AEDs. On this evaluation, information from a complete of 43 research have been included.
Valproic Acid (Depakote)
Prenatal publicity to valproic acid was related to a 2- to 4-fold elevated threat of autism spectrum dysfunction (ASD), a 2- to 5-fold elevated threat of mental incapacity (ID), a 1.5-fold elevated threat of ADHD, a 2- to 4-fold greater threat of analysis of emotional and behavioral issues, and poor adaptive functioning in comparison with offspring uncovered to different AEDs and unexposed controls.
The danger of hostile neurodevelopmental outcomes seems to be dose-dependent, with worse outcomes seen at doses of 900 mg per day or larger; nevertheless, some research have reported worse neurodevelopmental outcomes with imply each day doses as little as 600 to 750 mg.
Carbamazepine (Tegretol)
Throughout three cohort research, carbamazepine-exposed offspring had a better prevalence (12%–14%) of behavioral regulation issues in contrast with unexposed kids, characterised by aggression and hyperactivity. Findings of mental incapacity have been inconsistent.
Topiramate (Topamax)
Much less data is obtainable concerning neurodevelopmental outcomes in kids with prenatal publicity to topiramate. Of the ten research that included on this overview, 5 contained samples of lower than 10 topiramate-exposed offspring.
That stated, there’s a rising physique of proof indicating that prenatal publicity to topiramate could also be related to worse neurodevelopmental outcomes. A population-based examine together with 247 topiramate-exposed kids discovered a 2-fold elevated threat of ASD diagnoses and a 3.5-fold elevated threat of ID amongst topiramate-exposed offspring in contrast with unexposed offspring, notably in kids uncovered to doses above 100 mg each day.
One other current population-based examine of 290 topiramate-exposed offspring discovered a 2.38-fold elevated threat of ADHD in contrast with unexposed offspring.
Lamotrigine (Lamictal)
In comparison with unexposed offspring, lamotrigine-exposed offspring show comparable neurodevelopmental functioning. Potential cohort and population-based research have discovered no elevated threat of ASD diagnoses throughout samples together with over 15,000 exposures.
Not one of the 13 included research discovered proof of a dose-response relationship between lamotrigine and hostile neurodevelopmental outcomes.
Different Antiepileptic Medication
Proof for the remaining AEDs, together with gabapentin, pregabalin, lacosamide, zonisamide, clobazam, perampanel, ethosuximide, or brivaracetam, is missing.
Medical Implications
The present systematic overview confirms earlier research indicating worse neurodevelopmental outcomes associated to prenatal publicity to valproic acid, together with a 2- to 4-fold elevated threat of ASD, a 2- to 5-fold elevated threat of mental incapacity (ID), and a 2- to 4-fold greater threat of emotional and behavioral issues. This discovering, paired with the excessive threat of main malformations related to valproic acid, signifies that valproic acid must be prevented in ladies throughout being pregnant. And since half of all pregnancies are unplanned, these findings help the avoidance of valproic acid in all ladies of reproductive age.
There may be at the moment insufficient data on long-term neurodevelopmental outcomes in kids uncovered to different AEDs, equivalent to gabapentin and pregabalin. There may be, nevertheless, a rising literature to point that publicity to topiramate could also be related to worse neurodevelopmental outcomes, with one examine displaying a 2-fold elevated threat of ASD and and a 3.5-fold elevated threat of mental incapacity. These research point out that topiramate could carry related long-term dangers to valproic acid. As well as, it’s regarding that hostile outcomes have been noticed at a comparatively low dose of topiramate (100 mg).
This systematic overview helps the reproductive security of lamotrigine, indicating no improve in threat of hostile neurodevelopmental outcomes in kids uncovered to this AED throughout being pregnant.
Ruta Nonacs, MD PhD
References
Honybun E, Cockle E, Malpas CB, O’Brien TJ, Vajda FJ, Perucca P, Rayner G. Neurodevelopmental and Functional Outcomes Following In Utero Exposure to Antiseizure Medication: A Systematic Review. Neurology. 2024 Apr 23;102(8):e209175.
